PROJECTSUMMARY Understandinghowneuralcircuitsoperateandinterconnectatmesoscopic(sub-millimeter)scale,andhow neuroenergetic metabolism and neurotransmitters support brain function at resting and working state is essentialtobrainresearchandBRAINInitiative.Magneticresonance(MR)imaging(MRI),includingfunctional MRI (fMRI) and in vivo MR spectroscopic imaging (MRSI), is the sole modality enabling to imaging neural activity, functional connectivity and brain structure at cortical layer and column level, neuroenergetics and neurotransmitters in human brain. However, it remains challenging to address fundamental neuroscience questionsrequiringmuchhighersensitivityandspatiotemporalresolutioncurrentlyunavailable.IncreasingMR field strength has been the prevailing paradigm to tackle the challenge, however, beside high cost, it poses a safetyconcernfromelevatedspecificabsorptionrate(SAR)ofradiofrequency(RF)powerinthebraintissue. To address the technical challenges and limitations faced by the MR-based imaging techniques, we have pioneered an innovative and cost-effective engineering solution by introducing the ultra-high dielectric constant (uHDC) former incorporated with RF coils for large improvements of sensitivity and spatiotemporal resolution for fMRIandMRSI,andsynergisticallyreducingSARatultrahighfield(UHF).WiththeNIHR24fundingsupport,we have made progress with promising results for proof of concept. In this U01 proposal, we will further develop and integrate three advanced technologies: i) fixed and/or tunable uHDC formers incorporated with advanced RFcoiltechnologyformaximizingMRsensitivityandminimizingSAR;?ii)SPectroscopicImagingbyexploiting spatiospectral CorrElation (SPICE) technique for significantly boosting signal-to-noise ratio (SNR) and spatiotemporal resolution;? iii) UHF MR technology for further improving sensitivity and spectral resolution of MRSI.TheintegrationofthesetechnologieswillachievecumulativeandunprecedentedimprovementsatUHF and break current barriers of spatiotemporal resolution, ultimately enable i) ultrahigh-resolution fMRI mapping ofneuralactivity,circuitsanddynamics,andfunctionalconnectivityandnetworksatmesoscopicscaleat3and 7 tesla(T);? and ii) very high resolution and whole-brain multinuclear MRSI for functional mapping of neuroenergeticandneurotransmitterchangesinresponsetobrainstimulationatultrahighfields(7Tand10.5T) with an superior (?5mm isotropic) resolution comparable to conventional fMRI. The technology developments will be carried out by a consortium among interdisciplinary researchers from University of Minnesota, Penn State University and University of Illinois at Urbana-Champaign. Success of this project will usher the next generation of MR-based multimodal neuroimaging technology offering superior spatiotemporal resolution fully transformative for broad brain research, and generate comprehensive and high fidelity database of healthy humanbrainthatcanbesharedbyscientificcommunity.